tbuckley/cabot-search huggingface dataset:
Four Ounces Can Move a Thousand Pounds: The Enormous Value of Nanomaterials in Tumor Immunotherapy
Authors: Ziyin Chen, Ziqi Yue, Kaiqi Yang, Congrong Shen, Zhe Cheng, Xiaofeng Zhou, Shenglong Li
Journal: Advanced Healthcare Materials (2023)

Abstract The application of nanomaterials in healthcare has emerged as a promising strategy due to their unique structural diversity, surface properties, and compositional diversity. In particular, nanomaterials have found a significant role in improving drug delivery and inhibiting the growth and metastasis of tumor cells. Moreover, recent studies have highlighted their potential in modulating the tumor microenvironment (TME) and enhancing the activity of immune cells to improve tumor therapy efficacy. Various types of nanomaterials are currently utilized as drug carriers, immunosuppressants, immune activators, immunoassay reagents, and more for tumor immunotherapy. Necessarily, nanomaterials used for tumor immunotherapy can be grouped into two categories: organic and inorganic nanomaterials. Though both have shown the ability to achieve the purpose of tumor immunotherapy, their composition and structural properties result in differences in their mechanisms and modes of action. Organic nanomaterials can be further divided into organic polymers, cell membranes, nanoemulsion‐modified, and hydrogel forms. At the same time, inorganic nanomaterials can be broadly classified as nonmetallic and metallic nanomaterials. The current work aims to explore the mechanisms of action of these different types of nanomaterials and their prospects for promoting tumor immunotherapy.
Your Son Is a Very <i>Sick</i> Boy: What One Says Matters
Authors: Debra Normyle Mazza
Journal: JAMA (2023)

In this narrative medicine essay, a palliative care counselor identifies gaps in the meaning of common terms between the medical community and the loved ones of individuals with traumatic injuries by reflecting on her current work as a counselor in a trauma center and to her experiences after her son’s fatal car crash.
Metagenomic sequencing for investigation of a national keratoconjunctivitis outbreak, Israel, 2022
Authors: Yair Motro, Denise Wajnsztajn, Ayelet Michael-Gayego, Shubham Mathur, Roberto BM Marano, Ikram Salah, Chaggai Rosenbluh, Violeta Temper, Jacob Strahilevitz, Jacob Moran-Gilad
Journal: Eurosurveillance (2023)

Background Epidemics of keratoconjunctivitis may involve various aetiological agents. Microsporidia are an uncommon difficult-to-diagnose cause of such outbreaks. Aim During the third quarter of 2022, a keratoconjunctivitis outbreak was reported across Israel, related to common water exposure to the Sea of Galilee. We report a comprehensive diagnostic approach that identified Vittaforma corneae as the aetiology, serving as proof of concept for using real-time metagenomics for outbreak investigation. Methods Corneal scraping samples from a clinical case were subjected to standard microbiological testing. Samples were tested by calcofluor white staining and metagenomic short-read sequencing. We analysed the metagenome for taxonomical assignment and isolation of metagenome-assembled genome (MAG). Targets for a novel PCR were identified, and the assay was applied to clinical and environmental samples and confirmed by long-read metagenomic sequencing. Results Fluorescent microscopy was suggestive of microsporidiosis. The most abundant species (96.5%) on metagenomics analysis was V. corneae . Annotation of the MAG confirmed the species assignment. A unique PCR target in the microsporidian rRNA gene was identified and validated against the clinical sample. The assay and metagenomic sequencing confirmed V. corneae in an environmental sludge sample collected at the exposure site. Conclusions The real-time utilisation of metagenomics allowed species detection and development of diagnostic tools, which aided in outbreak source tracking and can be applied for future cases. Metagenomics allows a fully culture-independent investigation and is an important modality for public health microbiology.
Racial and Ethnic Disparities in Survival Among People With Second Primary Cancer in the US
Authors: Hyuna Sung, Lauren Nisotel, Ephrem Sedeta, Farhad Islami, Ahmedin Jemal
Journal: JAMA Network Open (2023)

Comprehensive data for racial and ethnic disparities after second primary cancers (SPCs) are lacking despite the growing burden of SPCs.To quantify racial and ethnic disparities in survival among persons with SPCs.This population-based, retrospective cohort study used data from 18 Surveillance, Epidemiology, and End Results registries in the US for persons diagnosed with the most common SPCs at age 20 years or older from January 1, 2000, to December 31, 2013 (with follow-up through December 31, 2018). Data were analyzed between January and April 2023.Race and ethnicity (Hispanic, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, and non-Hispanic White).The main outcomes were 5-year relative survival and cause-specific survival. Cause-specific hazard ratios (HRs) were calculated for death from cancer or cardiovascular disease (CVD) in each racial and ethnic minority population compared with the White population overall and stratified by SPC type, with adjustment for sex, year and age at SPC diagnosis, and prior cancer type and stage (baseline model) and additionally for county attributes (household income, urbanicity), SPC characteristics (stage, subtype), and treatment.Among 230 370 persons with SPCs (58.4% male), 4.5% were Asian or Pacific Islander, 9.6% were Black, 6.4% were Hispanic, and 79.5% were White. A total of 109 757 cancer-related deaths (47.6%) and 18 283 CVD-related deaths (7.9%) occurred during a median follow-up of 54 months (IQR, 12-93 months). In baseline models, compared with the White population, the risk of cancer-related death overall was higher in the Black (HR, 1.21; 95% CI, 1.18-1.23) and Hispanic (HR, 1.10; 95% CI, 1.07-1.13) populations but lower in the Asian or Pacific Islander population (HR, 0.93; 95% CI, 0.90-0.96). When stratified by 13 SPC types, the risk of cancer-related death was higher for 10 SPCs in the Black population, with the highest HR for uterine cancer (HR, 1.87; 95% CI, 1.63-2.15), and for 7 SPCs in the Hispanic population, most notably for melanoma (HR, 1.46; 95% CI, 1.21-1.76). For CVD-related death, the overall HR was higher in the Black population (HR, 1.41; 95% CI, 1.34-1.49), with elevated risks evident for 11 SPCs, but lower in the Asian or Pacific Islander (HR, 0.75; 95% CI, 0.69-0.81) and Hispanic (HR, 0.90; 95% CI, 0.84-0.96) populations than in the White population. After further adjustments for county attributes and SPC characteristics and treatment, HRs were reduced for cancer-related death and for CVD-related death and associations in the same direction remained.In this cohort study of SPC survivors, the Black population had the highest risk of both death from cancer and death from CVD, and the Hispanic population had a higher risk of death from cancer than the White population. Attenuations in HRs after adjustment for potentially modifiable factors highlight opportunities to reduce survival disparities among persons with multiple primary cancers.
Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Authors: Binghua Li, Yunzheng Li, Huajun Zhou, Yanchao Xu, Yajuan Cao, Chunxiao Cheng, Jin Peng, Huan Li, Laizhu Zhang, Ke Su, Zhu Xu, Yue Hu, Jiaming Lu, Yijun Lu, Liyuan Qian, Ye Wang, Yuchen Zhang, Qi Liu, Yuanyuan Xie, Sheng Guo, Wajahat Z. Mehal, Decai Yu
Journal: Hepatology (2023)

Background and Aims: Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy. Approach and Results: We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies. Conclusions: We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.
Emergence and potential transmission route of avian influenza A (H5N1) virus in domestic cats in Poland, June 2023
Authors: Lukasz Rabalski, Aleksandra Milewska, Anne Pohlmann, Karolina Gackowska, Tomasz Lepionka, Klaudiusz Szczepaniak, Agnieszka Swiatalska, Izabela Sieminska, Zbigniew Arent, Martin Beer, Marion Koopmans, Maciej Grzybek, Krzysztof Pyrc
Journal: Eurosurveillance (2023)

In June 2023, a fatal disease outbreak in cats occurred in Poland. Most cases tested in Poland (29 of 47) were positive for highly pathogenic avian influenza (HPAI) A (H5N1) virus. Genetic analyses revealed clade 2.3.4.4b with point mutations indicative of initial mammalian hosts adaptations. Cat viral sequences were highly similar (n = 21), suggesting a potential common infection source. To investigate possible infection routes, our group tested food samples from affected households. HPAI H5N1 virus was detected in one poultry meat sample.
LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress
Authors: Hongyang Huang, Yu-Man Tsui, Daniel Wai-Hung Ho, Clive Yik-Sham Chung, Karen Man-Fong Sze, Eva Lee, Gary Cheuk-Hang Cheung, Vanilla Xin Zhang, Xia Wang, Xueying Lyu, Irene Oi-Lin Ng
Journal: Hepatology (2023)

Background and Aims: HCC is an aggressive cancer with a poor clinical outcome. Understanding the mechanisms that drive tumor initiation is important for improving treatment strategy. This study aimed to identify functional cell membrane proteins that promote HCC tumor initiation. Approach and Results: Tailor-made siRNA library screening was performed for all membrane protein-encoding genes that are upregulated in human HCC (n = 134), with sphere formation as a surrogate readout for tumor initiation. Upon confirmation of membranous localization by immunofluorescence and tumor initiation ability by limiting dilution assay in vivo, LanC-like protein-1 (LANCL1) was selected for further characterization. LANCL1 suppressed intracellular reactive oxygen species (ROS) and promoted tumorigenicity both in vitro and in vivo. Mechanistically, with mass spectrometry, FAM49B was identified as a downstream binding partner of LANCL1. LANCL1 stabilized FAM49B by blocking the interaction of FAM49B with the specific E3 ubiquitin ligase TRIM21, thus protecting FAM49B from ubiquitin-proteasome degradation. The LANCL1-FAM49B axis suppressed the Rac1-NADPH oxidase-driven ROS production, but this suppression of ROS was independent of the glutathione transferase function of LANCL1. Clinically, HCCs with high co-expression of LANCL1 and FAM49B were associated with more advanced tumor stage, poorer overall survival, and disease-free survival. In addition, anti-LANCL1 antibodies targeting the extracellular N-terminal domain were able to suppress the self-renewal ability, as demonstrated by the sphere formation ability of HCC cells. Conclusions: Our data showed that LANCL1 is a cell surface protein and a key contributor to HCC initiation. Targeting the LANCL1-FAM49B-Rac1-NADPH oxidase-ROS signaling axis may be a promising therapeutic strategy for HCC.
Host genetic variation guides hepacivirus clearance, chronicity, and liver fibrosis in mice
Authors: Ariane J. Brown, John J. Won, Raphael Wolfisberg, Ulrik Fahnøe, Nicholas Catanzaro, Ande West, Fernando R. Moreira, Mariana Nogueira Batista, Martin T. Ferris, Colton L. Linnertz, Sarah R. Leist, Cameron Nguyen, Gabriela De la Cruz, Bentley R. Midkiff, Yongjuan Xia, Mia D. Evangelista, Stephanie A. Montgomery, Eva Billerbeck, Jens Bukh, Troels K.H. Scheel, Charles M. Rice, Timothy P. Sheahan
Journal: Hepatology (2023)

Background &amp; Aims: Human genetic variation is thought to guide the outcome of HCV infection, but model systems within which to dissect these host genetic mechanisms are limited. Norway rat hepacivirus, closely related to HCV, causes chronic liver infection in rats but causes acute self-limiting hepatitis in typical strains of laboratory mice, which resolves in 2 weeks. The Collaborative Cross (CC) is a robust mouse genetics resource comprised of a panel of recombinant inbred strains, which model the complexity of the human genome and provide a system within which to understand diseases driven by complex allelic variation. Approach &amp; Results: We infected a panel of CC strains with Norway rat hepacivirus and identified several that failed to clear the virus after 4 weeks. Strains displayed an array of virologic phenotypes ranging from delayed clearance (CC046) to chronicity (CC071, CC080) with viremia for at least 10 months. Body weight loss, hepatocyte infection frequency, viral evolution, T-cell recruitment to the liver, liver inflammation, and the capacity to develop liver fibrosis varied among infected CC strains. Conclusions: These models recapitulate many aspects of HCV infection in humans and demonstrate that host genetic variation affects a multitude of viruses and host phenotypes. These models can be used to better understand the molecular mechanisms that drive hepacivirus clearance and chronicity, the virus and host interactions that promote chronic disease manifestations like liver fibrosis, therapeutic and vaccine performance, and how these factors are affected by host genetic variation.
A comparison of double‐blind, placebo‐controlled food challenge and open food challenge
Authors: Frederik Bloch Jessen, Charlotte G. Mortz, Esben Eller, Julie H. Gudichsen, Emil A. Baekdal, Carsten Bindslev‐Jensen
Journal: Allergy (2023)

Abstract Background Double‐blind, placebo‐controlled food challenge (DBPCFC) remains the gold standard for diagnosing food allergy, despite sparse comparisons to open food challenges (OpenFCs). The objective of this retrospective study was to compare severity of symptoms and threshold values (cumulative dose of food allergen eliciting a clinical reaction) in children and adults with peanut allergy, challenged in an open and/or double‐blind, placebo‐controlled protocol. Methods This study included patients from the Allergy Centre, Odense University Hospital with a positive oral food challenge, defined as strict objective signs, with peanut during the period 2001–2022. Severity of symptoms was graded using the Sampson's severity score. Distribution models of threshold values were calculated using log‐normal interval‐censored survival analysis, and the number of placebo reactions was evaluated. Results In total, 318 positive OpenFCs and 86 DBPCFCs were included. There was no difference in severity of symptoms nor threshold values comparing the two challenge types, neither when stratified for age groups. However, a higher proportion of children experienced Grade 3 symptoms in the double‐blind group. Only one patient had a positive reaction to a placebo challenge. Conclusion Our findings do not advocate for DBPCFC being superior to OpenFC, if the latter is performed with strict objective stop criteria by trained staff.
Prognostic factors for primary cutaneous anaplastic large-cell lymphoma: a multicentre retrospective study from Japan
Authors: Tomomitsu Miyagaki, Norihito Inoue, Hiroaki Kamijo, Hikari Boki, Naomi Takahashi-Shishido, Hiraku Suga, Takatoshi Shimauchi, Eiji Kiyohara, Yoji Hirai, Kentaro Yonekura, Kengo Takeuchi, Makoto Sugaya
Journal: British Journal of Dermatology (2023)

The clinical implications of DUSP22 rearrangement and the association between DUSP22 rearrangement and lymphoid enhancer-binding factor 1 (LEF1) expression pattern in CD30+ cutaneous T-cell lymphomas (CTCLs) are unknown.This study assessed the incidence of DUSP22 rearrangement and its clinical and immunohistochemical implications in primary cutaneous anaplastic large-cell lymphoma (pcALCL), lymphomatoid papulosis (LyP) and CD30+ mycosis fungoides with large-cell transformation (MF-LCT), focusing especially on the association with the prognosis and LEF1 expression pattern. Prognostic factors of pcALCL were also examined.We conducted a multicentre retrospective study including patients with pcALCL, LyP and MF-LCT diagnosed between 1 January 2000 and 31 December 2018 in Japan. Baseline data at diagnosis, treatment course, overall survival (OS) and disease-specific survival (DSS) were collected. Immunohistochemical analysis and fluorescence in situ hybridization to detect DUSP22 and TP63 rearrangement were performed using skin samples at diagnosis. We investigated the association between staining pattern and these gene rearrangements. We also assessed the prognostic implications of clinical status, immunohistochemical results and the presence of gene rearrangements.DUSP22 rearrangement was detected in 50% (11 of 22) of cases of pcALCL, but not in any cases with LyP (0 of 14) or MF-LCT (0 of 11). TP63 rearrangement was not detected in any case. Clinically, patients with pcALCL with DUSP22 rearrangement did not tend to develop ulcers (P = 0.081). There was no significant association between DUSP22 rearrangement status and immunohistochemical results, including LEF1 expression pattern. T3 stage and the presence of lower limb lesions were significantly associated with shorter OS (P = 0.012 and 0.021, respectively, by log-rank test). Similarly, they were significantly correlated with shorter DSS (P = 0.016 and 0.0001, respectively).DUSP22 rearrangement is relatively specific to pcALCL among CD30+ CTCLs in Japan. Although the LEF1 expression pattern was not related to DUSP22 rearrangement in pcALCL, there was no rearrangement if LEF1 was not expressed. We confirmed that T3 stage and the lower limb involvement were significantly associated with decreased OS and DSS. The presence or absence of lower limb lesions should be included in T-stage subcategorization in the future.
Extracellular vesicle-embedded materials
Authors: Yingchang Ma, Steve Brocchini, Gareth R. Williams
Journal: Journal of Controlled Release (2023)

Extracellular vesicles (EVs) are small membrane-bound vesicles released by cells. EVs are emerging as a promising class of therapeutic entity that could be adapted in formulation due to their lack of immunogenicity and targeting capabilities. EVs have been shown to have similar regenerative and therapeutic effects to their parental cells and also have potential in disease diagnosis. To improve the therapeutic potential of EVs, researchers have developed various strategies for modifying them, including genetic engineering and chemical modifications which have been examined to confer target specificity and prevent rapid clearance after systematic injection. Formulation efforts have focused on utilising hydrogel and nano-formulation strategies to increase the persistence of EV localisation in a specific tissue or organ. Researchers have also used biomaterials or bioscaffolds to deliver EVs directly to disease sites and prolong EV release and exposure. This review provides an in-depth examination of the material design of EV delivery systems, highlighting the impact of the material properties on the molecular interactions and the maintenance of EV stability and function. The various characteristics of materials designed to regulate the stability, release rate and biodistribution of EVs are described. Other aspects of material design, including modification methods to improve the targeting of EVs, are also discussed. This review aims to offer an understanding of the strategies for designing EV delivery systems, and how they can be formulated to make the transition from laboratory research to clinical use.
Targeting MDM2 in Soft-Tissue Sarcomas (and Other Solid Tumors): The Revival?
Authors: Antoine Italiano
Journal: Cancer Discovery (2023)

Summary: Murine double minute 2 (MDM2) inhibitors represent an opportunity to target p53 in solid tumors with wild-type TP53 and particularly in some sarcomas characterized by a consistent amplification of the MDM2 gene. In this issue of Cancer Discovery, LoRusso and colleagues and Koyama and colleagues report the results of two early-phase studies investigating two different TP53–MDM2 antagonists in patients with soft-tissue sarcomas and other solid tumors. See related article by LoRusso et al., p. 1802 (5) . See related article by Koyama et al., p. 1814 (8) .
Topical corticosteroids inhibit allergic skin inflammation but are ineffective in impeding the formation and expansion of resident memory T cells
Authors: Emi Ono, Vanina Lenief, Marine‐Alexia Lefevre, Roxane Cuzin, Aurélie Guironnet‐Paquet, Amandine Mosnier, Audrey Nosbaum, Jean‐Francois Nicolas, Marc Vocanson
Journal: Allergy (2023)

Abstract Background Tissue‐resident memory T (T RM ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease. Methods We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal T RM cells in a preclinical model of ACD to 2,4‐dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ T RM by flow cytometry and RNA sequencing. Results The impact of TA on T RM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of T RM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of T RM . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T RM , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T RM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T RM re‐expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications. Conclusions Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen‐specific T RM , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.
The interplay of quaternary ammonium lipid structure and protein corona on lung-specific mRNA delivery by selective organ targeting (SORT) nanoparticles
Authors: Sean A. Dilliard, Yehui Sun, Madeline O. Brown, Yun-Chieh Sung, Sumanta Chatterjee, Lukas Farbiak, Amogh Vaidya, Xizhen Lian, Xu Wang, Andrew Lemoff, Daniel J. Siegwart
Journal: Journal of Controlled Release (2023)